Integrated analysis of safety data from 12 clinical interventional studies of plasma- and albumin-free recombinant factor VIII (rAHF-PFM) in haemophilia A.

INTRODUCTION: Antihaemophilic factor (recombinant), plasma/albumin-free method (rAHF-PFM) is a human recombinant full-length factor VIII (FVIII) approved worldwide for the control and prevention of bleeding episodes, routine prophylaxis and perioperative management in adults and children with haemophilia A.

AIM: To evaluate rAHF-PFM safety [including adverse events (AEs) and inhibitor incidence] from 12 interventional studies spanning >10 years.

METHODS: The study population comprised 418 treated patients (median age = 18.7 years) with FVIII levels ≤2% of normal, including 55 previously untreated or minimally treated patients (PUPs/MTPs) from all rAHF-PFM phase I-IV studies, excluding observational safety studies.

RESULTS: Most AEs were non-serious; only 93 AEs in 45 patients (10.8%) were related to rAHF-PFM. A total of 106 serious AEs (SAEs) occurred in 69 patients (16.5%); the most common were FVIII inhibitors (4.1%), device-related infection (1.0%) and pyrexia (0.7%). The 17 SAEs considered related to treatment consisted of FVIII inhibitors in 1 previously treated patient (PTP) (≤5 Bethesda Units [BU]) and 16 PUPs/MTPs [7/55 high titre (>5 BU), 12.7%; 9/55 low titre (≤5 BU), 16.4%]. Overall, the incidence of FVIII inhibitors was 0.36% in PTPs and 29.1% in PUPs/MTPs. No deaths or cases of hypersensitivity related to rAHF-PFM occurred.

CONCLUSION: This integrated safety analysis evaluated the safety and tolerability of rAHF-PFM in children and adults with moderately severe or severe haemophilia A in all interventional studies completed to date. It was important to review consolidated evidence as some AEs are rare. There were no new safety signals in a wide variety of clinical settings.